Entropy-Driven Intramolecular Cross-Linking of Polymers near the Solubility Limit

Single-chain nanoparticles (SCNPs) are well-defined nanoscale objects formed through the intramolecular cross-linking of individual polymer chains. A longstanding challenge in this field is the inability to synthesize SCNPs at high concentrations, an essential requirement for scalable production and practical applications. Here, we introduce an entropy-driven strategy that enables one-pot preparation of both noncovalently and covalently cross-linked SCNPs at concentrations approaching the polymer’s solubility limit, on the order of grams per milliliter, far exceeding previously reported conditions by orders of magnitude. This method is straightforward and efficient, requiring neither polymer modification nor complex processing steps, and is broadly applicable to homopolymers, block copolymers, and random copolymers with high molecular weights. Our findings break the conventional concentration barrier in SCNP synthesis and provide a general framework for the design of next-generation single-chain nanostructures.